tbuckley/cabot-search huggingface dataset:
Real-world treatment patterns and sequencing in patients with locally advanced or metastatic urothelial cancer (la/mUC) in the US.
Authors: Mairead Kearney, Hamid Mahmoudpour, Chiemeka Ike, Ambar Modh, Sebastian Monzon, Matina Fragkogianni, Ken Carson
Journal: Journal of Clinical Oncology (2023)

572 Background: Platinum-based chemotherapy (PBC) is standard first-line (1L) treatment (tx) for patients (pts) with la/mUC. On June 30, 2020, avelumab was approved in the US as 1L maintenance (1LM) for pts without disease progression following PBC. Other novel agents such as enfortumab vedotin were recently approved for second-line (2L) or later tx. Little is known about how to incorporate these agents into the optimal tx sequencing approach. This real-world (RW) study describes the characteristics and tx patterns of pts with la/mUC. Methods: A retrospective cohort of de-identified records of pts with la/mUC was obtained from the Tempus Database. Eligible pts were diagnosed with la/mUC between January 1, 2016 and February 23, 2022. Pts who completed 1L PBC were categorized as 1LM or 2L-treated. 1LM was differentiated from 2L tx based on stated clinical intent of 1LM or initiation of immunotherapy (IO) within 180 days of 1L PBC completion without disease progression. These patients were split into pre and post groups based on when they completed their 1L PBC in relation to avelumab 1LM US approval on June 30, 2020. Results: A total of 821 pts were included from community centers (21%), academic centers (27%), and ASCO CancerLinQ network sites (52%). The median age at diagnosis was 68 years (IQR, 61-75), 73% male, and 63% White. 634 (77%) pts received 1L systemic tx; of those, 62% (395/634) received PBC, 24% (155/634) received IO monotherapy, 7% (45/634) received non-PBC, and 6% (39/634) received other regimens. Tx sequencing for a subgroup of pts who discontinued 1L PBC pre- and post-avelumab 1LM approval is shown (Table). Of those receiving IO (n=84) as subsequent tx post-avelumab approval, 80% (67/84) received IO as 1LM, out of which, 84% (56/67) received avelumab as 1LM. Of the 25 pts who received 2L tx after progression on IO 1LM post-avelumab approval, enfortumab vedotin was the most commonly integrated 2L agent (n=20; 80%). Conclusions: This RW study offers valuable insight into the characteristics of pts with la/mUC treated in routine clinical practice in the US. These tx pattern data are consistent with known and evolving tx paradigms in la/mUC. In subsequent RW studies, clinical data with longer follow-up could provide further insight into the optimal tx sequencing and associated clinical outcomes. [Table: see text]
Biochemical disease control outcomes of stereotactic body radiation therapy (SBRT) or moderate hypo-fractionation (HFRT) for low- and intermediate-risk prostate cancer (PrCa): Retrospective analysis of 12 years of experience at two Canadian cancer centers.
Authors: Hsin-pei (Spencer) Hu, Mohammad Gouran-Savadkoohi, Gregory Anagnostopoulos, Ian S. Dayes, Adrian Ishkanian, Abhirami Hallock, Thomas B Corbett, Himanshu Lukka, Kimmen Quan, Kara Schnarr, David Cuthbert, Mira Goldberg, Theodoros Tsakiridis
Journal: Journal of Clinical Oncology (2023)

363 Background: SBRT uses highly conformal radiotherapy to deliver high dose per fraction treatment. Advantages of SBRT include short treatment times, decreased costs and limited toxicity. Randomized trial outcomes of 7-fraction SBRT for low or intermediate PrCa were reported but results of studies that compared 5-fraction SBRT with conventional and HFRT are pending. Here, we reviewed the 12-year experience with SBRT and HFRT at the Juravinski and Walker Family Cancer Centers in Ontario. Methods: We reviewed patients with low or intermittent-risk PrCa treated with SBRT alone or HFRT alone in the period of July 2010 and February 2022. Database search criteria included treatments with SBRT 35-40Gy in 5 fractions and HFRT 60-62Gy in 20 fractions. Overall survival (OS), time to biochemical failure (per Phoenix criteria: i.e., 2ng/mL above PSA nadir) and biochemical failure-free survival (bFFS) were reviewed. Kaplan-Meier curves were used to assess OS and bFFS. Results: We identified 314 patients with low or intermediate-risk PrCa who were treated with SBRT and 258 patients who were treated with HFRT. Intermediate-risk category composed 86.0% and 95.7% of the SBRT and HFRT cohorts. ISUP Grade Group (GG) distributions for the SBRT and HFRT patients were: GG1: 19.4% and 9.3%, GG2: 72.9% and 74.0%, and GG3: 7.6% and 16.7%, respectively. OS rates at 5 years were 96.6% for SBRT vs. 95.8% for HFRT-treated patients. The 5-year bFFS rates for SBRT and HFRT were 92.3% and 90.1%, respectively. The 7-year bFFS rate for the SBRT cohort was 90.2%. Mean time to biochemical failure was 40.4 months after SBRT vs. 35.8 months after HFRT. Conclusions: SBRT is an effective treatment option for low to intermediate-risk PrCa with encouraging OS and bFFS rates comparable with HFRT. Pending randomized trial results will determine whether SBRT is the new standard of care for this population.
Social determinants of health (SDOH) and survival among patients with metastatic prostate cancer (mPC): A systematic literature review (SLR).
Authors: Stephen J. Freedland, Alexander Niyazov, Jonathan Nazari, Evelyn Worthington, Austin Lansing, Emily Rosta, Imtiaz Samjoo
Journal: Journal of Clinical Oncology (2023)

25 Background: Population level data show strong associations between race and other SDOH including income, education, and geographic region of residence. The relationship between SDOH and clinical outcomes has become increasingly recognized. This review examines the impact of SDOH on survival in patients with mPC in real-world (RW) settings. Methods: A systematic literature search in accordance with Cochrane guidelines was conducted on July 7, 2022, searching for RW studies published as full-text (Jan 2012-July 2022) and conferences (Jan 2019-July 2022) using Ovid MEDLINE, Embase, and Cochrane. A manual search of key congress websites for conference abstracts was also conducted. Studies which assessed the impact of SDOHs on survival, treatment access, and other clinical outcomes in patients with mPC were included in the overall SLR. Here, we present results from studies which assessed the impact of SDOH on overall survival (OS) and prostate cancer specific mortality (PCSM). Clinical trials were excluded. Results: Of 3,228 records screened, 86 studies were included, with findings reported in 67 full-text publications (60 US and 7 ex-US) and 28 conference abstracts (22 US and 6 ex-US). The impact of race on survival was reported in 54 studies. While most studies showed no difference between Black vs White for both OS (n=22) and PCSM (n=8), for patients on specific mPC treatments, there was an association between Black race and improved OS (n=5). Asian patients had improved OS vs White patients (n=4), and reduced PCSM vs White (n=6) and Black patients (n=1). Higher income was generally associated with improved OS (n=7), but no difference in PCSM (n=3). Although the regions compared differed, most studies found disparities in OS among US geographic regions (n=5). Education level was generally not associated with OS (n=2) or PCSM (n=3). Most studies showed that married patients had improved OS (n=4) and reduced PCSM (n=3) compared to unmarried patients. Conclusions: This SLR demonstrated that various SDOH are associated with disparities in survival among mPC patients. Asian race, which is generally associated with higher frequency of better SDOH risk factors, was linked with better OS. In contrast, Black race, which is generally associated with higher frequency of worse SDOH risk factors, was associated with similar or better OS. Having lower income and being unmarried were both associated with reduced OS, while disparities in OS were reported across geographic regions of the US. More studies are needed to understand why SDOH are linked with poor outcomes, including their connection with access to care.
Predictive accuracy of computer-generated C-index nephrometry scores compared with human-generated scores in predicting oncologic and perioperative outcomes.
Authors: Andrew Wood, Tarik Benidir, Nour Abdallah, Nicholas Heller, Fabian Isensee, Resha Tejpaul, Chalairat Suk-ouichai, Caleb Curry, Alex You, Erick M. Remer, Samuel Haywood, Steven Campbell, Nikolaos Papanikolopoulos, Christopher J. Weight
Journal: Journal of Clinical Oncology (2023)

623 Background: The Centrality index (C-index) score is a validated nephrometry scoring system that requires precise measurements and mathematical calculations of cross sectional imaging. Like other nephrometry scores, its implementation has been slowed by required time investment and interobserver variability. We sought to automate this score on preoperative computerized tomography scans by developing an artificial intelligence-generated C-index score. We then aimed to evaluate its ability to predict meaningful oncologic and perioperative outcomes as compared to human-generated C-index nephrometry scores. Methods: 300 patients with preoperative computerized tomography with early arterial contrast phase were identified from a cohort of 544 consecutive patients undergoing surgical extirpation for suspected renal cancer. A deep neural network approach was used to automatically segment kidneys and tumors, and then programed to generate the measurements and calculate C-index score. Human C-index scores were independently calculated by medical personnel blinded to AI-scores. AI- and Human score agreement was assessed using bivariate linear regression correlation and their predictive abilities for both oncologic and perioperative outcomes were assessed using logistic regression and compared with receiver operating characteristic (ROC) curve analyses with measurements of areas under the curve (AUC). Results: Median age was 60 years (IQE 51–68), and 40% were female. Median tumor size was 4.2 cm and 91.3% had malignant tumors. 27% were high stage, 37% high grade, and 63% underwent partial nephrectomy. There was significant agreement between Human scores and AI-scores on linear regression analysis (R 2 = 0.738, p &lt;0.0001). Both AI- and Human generated C-index scores similarly predicted meaningful oncologic outcomes, with lower levels of either C-index score associated with increased risk of malignant histology (H-score p = 0.018, AI score p =0.014) high-grade disease (both p &lt;0.0001), and high stage disease (both p &lt;0.0001). Lower levels of either AI or human generated C-index scores also predicted a radical nephrectomy rather than partial nephrectomy surgical approach (both p &lt;0.0001). AUC measurements (Table) were similar but consistently superior for AI generated C-index scores. Conclusions: Fully automated AI-generated C-index scores are comparable to human-generated C-index scores and predict a wide variety of meaningful patient-centered outcomes. Once validated in additional populations, our results suggest that our AI generated C-index could be delivered automatically from a preoperative CT scan to a clinician and patient at the point of care to aid in decision making. [Table: see text]
Treatment and survival of de novo metastatic prostate cancer in US veterans.
Authors: Martin W. Schoen, Ruth Douglas Etzioni, Eric Marshall Knoche, Julie N Graff, Kristen Marie Sanfilippo, Suhong Luo, Seth A Eisen, Robert Bruce Montgomery
Journal: Journal of Clinical Oncology (2023)

87 Background: Combination therapies using the androgen deprivation therapy (ADT) backbone have revolutionized treatment of metastatic hormone sensitive prostate cancer (mHSPC). Combinations include ADT plus docetaxel (DOC) or the androgen receptor targeting agents (ARTAs) abiraterone (AA), enzalutamide (ENZ), apalutamide (APA), and darolutamide (DAR). This study evaluates the utilization of these therapies in de novo mHSPC in a cohort of veterans and assesses recent overall survival (OS) of these therapies. Methods: Veterans were identified from 2012-2021 in the Veterans Affairs Prostate Cancer Data Core (VAPC) and oncology tumor registries using the initial pathological diagnosis of prostate cancer with SEER stage ‘distant’. All veterans had ADT initiated within 1 month prior and 3 months after diagnosis in VAPC. Additional therapies including DOC or ARTAs were collected from VAPC if initiated from 1 month prior to 4 months after ADT initiation. Data cut point was June 2022. Results: 5,006 patients with de novo mHSPC were identified with median age of 73.1 years (yrs), and 1338 (26.7%) identified as Black race. From 2012 to 2021, ADT alone was used in 3,569 (71.3%) of veterans, DOC in 438 (8.7%) and ARTAs in 999 (20.0%), wherein use of different ARTAs was AA in 783 (78.4%), ENZ in 204 (20.4%), APA in 10 (1.0%), and DAR in 2 (0.2%). Use of combination therapy for mHSPC increased from 3.1% in 2012-2013 to 61.2% in 2020-2021. Use of DOC peaked in 2016 and was used in 16.3% of veterans that year. Veterans treated with DOC were significantly younger (median 67.3 yrs, p&lt;0.001) compared to veterans treated with ARTAs (73.1 yrs) or ADT alone (74.3 yrs). Veterans treated with combination therapies had longer median OS compared to ADT alone (37.2 vs. 29.3 months, p&lt;0.001), with no significant difference between DOC and ARTA combinations (p=0.84). For 2,042 veterans with de novo mHSPC treated from 2018-2021, median OS of veterans treated with ADT+DOC (n=161, 35.3 months) and ADT+ARTA (n=849, 41.2 months) was longer than ADT alone (n=1,032, 29.3 months, p&lt;0.001). There was no significant difference in median OS between DOC and ARTA combinations in this group (p=0.69). Conclusions: In veterans presenting with de novo mHSPC, use of initial combination therapy has increased, with the majority of veterans treated with ADT and an ARTA in 2020-2021. In this cohort, combination therapy was associated with longer OS compared to ADT alone and no significant differences were found between type of combination and OS. [Table: see text]
Disparities in germline testing by race/ethnicity and preferred language in patients with prostate cancer.
Authors: Annelise Thorn, Kelly Gordon, Barry Tong, Daniel H Kwon, Mallika Sachdev Dhawan, Hala Borno, Rahul Raj Aggarwal, Eric Jay Small, Amie Blanco
Journal: Journal of Clinical Oncology (2023)

112 Background: A remote Genetic Testing Station (GTS) workflow was implemented at an academic medical institution to expand access to genetic testing for patients with prostate cancer. During a telephone appointment, a genetic counselor assistant collects family history and facilitates genetics education, research consent, and remote sample collection for multi-gene panel testing. We compared testing completion and patient loss from workflow based on race/ethnicity and preferred language to identify disparities. Methods: Metrics were collected prospectively and analyzed retrospectively for patients with metastatic or high-grade prostate cancer referred to genetics between 3/15/2020 – 6/30/2022. Self-reported race, ethnicity, and preferred language were collected by chart review. Testing completion was compared between groups using Fisher’s exact test, with White non-Hispanic (WNH) and Preferred Language English (PLE) cohorts as controls. Odds ratios and 95% confidence intervals were reported. Patient loss at workflow checkpoints (scheduling, consenting, sample collection, and results release) was summarized for each group. Results: 827 eligible patients were identified: 78 (9%) Asian /Pacific Islander (API), 51 (6%) Black non-Hispanic (BNH), 42 (5%) Hispanic, and 625 (76%) WNH. 31 patients reporting other non-Hispanic race were not included in the analysis. 30 patients (4%) self-reported Preferred Language non-English (PLNE) and 797 (96%) PLE. BNH patients were significantly less likely to complete testing compared to WNH patients (OR 0.320, 95%CI: 0.168, 0.632, p&lt;0.001). There was no difference in testing completion in API (OR 0.918, 95%CI: 0.467, 1.944, p=0.797) or Hispanic (OR 0.743, 95%CI: 0.325, 1.918, p=0.466) compared to WNH patients. PLNE were significantly less likely to complete testing (OR 0.393, 95%CI: 0.171, 0.965, p=0.016) compared to PLE patients. Patient loss occurred primarily at consenting and sample collection. 14% of BNH, and 9% of Hispanic patients did not consent, compared to 4% of WNH. 17% of PLNE did not consent compared to 5% of PLE patients. 13% of BNH did not return a sample, compared to 3% of WNH patients. Conclusions: In remote GTS, BNH and PLNE patients were significantly less likely to complete germline testing than WNH and PLE patients respectively. Disparities in patient loss were most pronounced at consenting and sample collection. Measures to mitigate disparities include assisted consenting (with interpreter as needed) and video-assisted or in-clinic sample collection. [Table: see text]
Correlation of age and the tumor transcriptomic profile in patients (pts) with advanced prostate cancer (PCa).
Authors: Kamal Kant Kant Sahu, Yeonjung Jo, Beverly Chigarira, Jong Taek Kim, Nicolas Sayegh, Georges Gebrael, Nishita Tripathi, Shruti Adidam Kumar, Vinay Mathew Thomas, Haoran Li, Roberto Nussenzveig, Manish Kohli, Sumati Gupta, Benjamin L. Maughan, Neeraj Agarwal, Umang Swami
Journal: Journal of Clinical Oncology (2023)

233 Background: In general, older pts are likely to have an advanced stage PCa, hence poor overall survival (PMID: 18660852). Owing to increased awareness and better diagnostics, the incidence of PCa has steadily increased amongst older adolescents and young adult pts (PMID: 31553489). Recent reports suggest that younger pts often are staged less adequately, present with more advanced stages, and could have worse outcomes than older pts (PMID: 33575208). Hence, elucidating the underlying molecular biology of PCa by age may unravel specific biologic features and distinct genomic expressions specific to young-age PCa, and help investigate new therapeutic targets. Methods: In this IRB-approved retrospective study, eligibility criteria included pts diagnosed with advanced PCa with available tumor-based comprehensive transcriptomic profiling from a CLIA-certified lab. DeSeq2 analysis was implemented in Bioconductor software to analyze differentially expressed genes based on the cohort's age cut-off points (&lt; 65 vs. ≥65 years). DeSeq2 results included the Log2 Fold change, Wald-Test p-values, and Benjamini-Hochberg adjusted p-values for each differentially expressed gene. These results were then subjected to Gene Set Enrichment Analysis (GSEA) to identify pathways upregulated or downregulated in each cohort. All bioinformatic analysis was conducted in R-Studio, version 4.1.1. The statistical significance level was predetermined at 0.05. Results: 80 pts were eligible: &lt; 65 (n=44) vs ≥65 years (n=36). No differences in Gleason score (&lt;8/≥8), baseline PSA levels, and disease volume (high/low) between the cohorts (Table). As compared to pts ≥65 years; in young pts, (1) the three most upregulated significant pathways were oxidative phosphorylation (OXPHOS), bile acid, and fatty acid metabolism pathways, and (2) the three most downregulated significant pathways were tumor necrosis factor-alpha (TNFα) via NF-Κb, transforming growth factor-β (TGF β), and inflammatory response pathways. Differential individual gene expression profiles will be presented at the meeting. Conclusions: These hypothesis-generating data show distinct genomic pathways to be upregulated in younger pts vs. older pts with advanced PCa and may guide further drug development, e.g., OXPHOS inhibitors in younger pts vs. drugs targeting inflammatory response in older pts. These hypothesis-generating results, upon external validation, may provide the rationale for personalized therapy in pts with PCa. [Table: see text]
Real-world time-to-castration resistance (CR) among patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) initiating apalutamide (APA), enzalutamide (ENZ), or abiraterone acetate (ABI) from an oncology database.
Authors: Benjamin H Lowentritt, Carmine Rossi, Shawn Du, Erik Muser, Frederic Kinkead, Dexter Waters, Patrick Lefebvre, Dominic Pilon, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2023)

65 Background: CR is an important clinical indicator of disease progression and worsening overall survival among pts with mCSPC. This study describes real-world time-to-CR progression in an oncology setting among pts with mCSPC who initiated APA, ENZ, or ABI in the United States. Methods: Clinical data from the Flatiron Metastatic Prostate Cancer (PC) Core Registry Electronic DataMart (1/1/2013 – 07/31/2022) were evaluated. Metastatic pts without evidence of CR before initiating a next-generation androgen inhibitor (AAI) were classified into exclusive treatment cohorts based on the start date (index date) for APA, ENZ, or ABI. CR was identified by a Flatiron algorithm searching for: 1) mention of CR in patient charts, 2) rising prostate-specific antigen (PSA) levels documented from laboratory testing, or 3) mention of rising PSA while on hormonal therapy from unstructured data sources. Pts had ≥12 months (mo) of clinical data pre-index date and were followed from the index date until the end of clinical activity (including death) or data availability. The proportion of pts developing CR was described separately for each cohort using Kaplan-Meier analysis up to 24 mo post-index, with no adjustment for baseline confounders. CR progression rates in the current analysis were descriptively compared to those observed in Phase 3 trials where available. Results: A total of 155 APA, 385 ENZ and 711 ABI pts were evaluated. Mean age at index was ~73 years in each group. Mean follow-up was 12.8 mo (APA), 13.4 mo (ENZ) and 20.6 mo (ABI). Use of androgen deprivation therapy prior to initiation of AAI was observed in ~85% of pts. The median time between documented metastasis and the index date was 2.3 mo (APA), 2.8 mo (ENZ), and 2.3 mo (ABI). Progression rates to CR are shown. By 24 mo, the median time-to-CR was not reached with any treatment studied. By 24 mo, progression to CR was observed in 26% of APA pts in this analysis (32% in TITAN); 36% of ENZ pts in this analysis (25% in ARCHES); and 33% of ABI pts in this analysis (progression to CR not reported in LATITUDE). Conclusions: In this real-world database, the observed proportions of pts progressing to CRPC for the APA and ENZ cohorts were generally consistent with results of Phase 3 trials and include a small proportion of pts with early progression to CRPC. Increased physician awareness of the benefits of early initiation of an AAI along with identification of baseline biomarkers associated with early progression to CRPC may improve clinical outcomes. [Table: see text]